Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

"Conflict of interest statement The first author was renumerated by IMMPACT for their work at the consensus meeting and in drafting the manuscript. The project was supported by ACTTION, a public–private partnership. The views expressed in this article are those of the authors and no official endorsement by the Food and Drug Administration (FDA) or the pharmaceutical and device companies that provided unrestricted grants to support the activities of the ACTTION public–private partnership should be inferred. Individual authors' declarations of potential conflicts of interest are as follows: M. J. Bair reports grants or contracts from VA Health Services Research and Development, VA Cooperative Studies Program, and National Endowment for the Arts and participation on a Data Safety Monitoring Board or Advisory Board on a NIH project conducted at the University of Utah. This trial is a pragmatic trial of physical therapy intervention. Prof Cherkin reports being paid an honorarium for mentoring the first author with manuscript writing. L. L. DeBar reports support for the present manuscript from Kaiser Permanente Washington Health Research Institute (KPWHRI); grants and contracts from National Institutes of Health (NIH) and Patient-Centered Outcomes Research Institute (PCORI); an honorarium for a lecture at 2020 IMMPACT Consensus Meeting; support for attending meetings from KPWHRI and NIH; and participation on a Data Safety Monitoring Board or Advisory Board for NCCIH, BACPAC DSMB. P. Cowan is the co-founder and secretary of the World Patients Alliance and Board Member Emeritus as well as Founder of the American Chronic Pain Association. P. Desjardins reports grants or contracts from the NIH/NIDCR Opioid Analgesic Reduction Study as co-investigator; consulting fees from Acadia Pharmaceuticals, GlaxoSmithKline Consumer Healthcare, Neurana Pharmaceuticals, Bayer Consumer Healthcare, Senju USA, Antibe Therapeutics, and CenExel; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer Consumer Healthcare; participation on the GSK Consumer Advisory Board; and roles on the Board of Directors of ProSelect/Coverys Medical Liability Insurance and the Board of Governors of South Orange Performing Arts Center. R. H. Dworkin has received in the past 5 years research grants and contracts from the U.S. Food and Drug Administration and the U.S. National Institutes of Health, and compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CombiGene, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, GlaxoSmithKline, Glenmark, Gloriana, Grace, Hope, Hospital for Special Surgery, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, Orion, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG. R. R. Ewards reports no conflicts of interest. J. T Farrar reports grants or contracts from the NIH-NCATS-UL1 Grant (Co-I), FDA-BAA Contract, NIH-NIDDK-U01 Grant (CoI), and NIH-NINDS-U24 Grant (PI); consulting fees from Lilly and Vertex Pharma; participation on a Data Safety Monitoring Board or Advisory Board for NIH-NIA(DSMB); and a role as President-Elect US-ASP. M. Ferguson reports grants or contracts from ACTTION paid to her institution for work on systematic reviews and payment or honoraria for lectures at IMMPACT meetings from ACTTION. R. Freeman reports consulting fees from AlgoRx, Allergan, Applied Therapeutics, Clexio, Collegium, Cutaneous NeuroDiagnostics, Glenmark, GW Pharma, GlaxoSmithKline, Eli Lilly, Lundbeck, Maxona, Novartis, NeuroBo, Regenacy, Vertex, and Worwag and stock options in Cutaneous Neurodiagnostic Life Sciences, NeuroBo, Maxona, and Regenacy. J. S. Gewandter reports grants or contracts from the NIH; consulting fees from AlgoTX, GW Pharma, Magnolia Neurosciences, Orthogonal, Science Branding Consulting, AKP Pharma, and Eikonizo and support for attending meetings or travel from SOPATE and INS. I. Gilron declares a travel stipend to attend ACTTION meeting 2019 and reports consulting fees from CombiGene, GW Research, Lilly, and Novaremed. H. Grol-Prokopczyk reports grants or contracts from the National Institute on Aging of the National Institutes of Health, Award #R01AG065351; honoraria for an invited lecture for Multidisciplinary Research in Gerontology Colloquium Series, University of Southern California, and for an invited lecture at Napa Pain Conference; and travel reimbursement for travel to Napa Pain Conference. S. H. Hertz declares consulting fees from Adial Pharmaceuticals, AIXThera Operations Limited, Asahi Kasei Pharma America Corporation, Allay Pharmaceuticals, Amygdala Neurosciences, Araim Pharmaceuticals, Artugen Therapeutics, Avenue Therapeutics, BioQ Pharma, Cali Pharmaceuticals, Celero Pharma, Centrexion Therapeutics, Collegium Pharmaceutical, Concentric Analgesics, Currax Pharmaceuticals, Delpor, Domain Therapeutics, Enalare Therapeutics, Go Medical Industries, Heron Pharmaceuticals, Innocoll Biotherapeutics, Intra-Cellular Therapies, Kaleo, Lyndra Therapeutics, Maxona Pharmaceuticals, MDI Pharma, Nema Research, Neuroderm, Neumentum, Novilla Pharmaceuticals, OncoZenge, Pfizer, PleoPharma, SafeRx Pharmaceuticals, The Scripps Research Institute, Sollis Therapeutics, Sparian Biosciences, Teikoku Pharma USA, Taiwan Liposome Company, Tremeau Pharmaceuticals, Vallon Pharmaceuticals, Vizuri Health Sciences, and WinSanTor. D. G. Hohenschurz-Schmidt reports support for the present manuscript from a PhD studentship by the Alan and Sheila Diamond Charitable Trust and a honorarium from IMMPACT; a research grant from The osteopathic Foundation (paid to institution); consulting fees from Altern Health Ltd; and the role of executive committee member of the Society for Back Pain Research. S. Iyengar reports employment and travel support from the NINDS/NIH; stock options in Retiree and Eli Lilly and Company; and other financial or nonfinancial interests through employee of NINDS/NIH and adjunct senior research professor, Indiana University School of Medicine, Departments of Anesthesia and Clinical Pharmacology. C. Kamp reports support for the present manuscript from ACTTION, FDA contract #HHSF223201000078C, with payments made directly to her institution, University of Rochester Medical Center, providing 5% salary support and consulting fees from Clintrex Research Corporation (payments made to her consulting company CLKamp Consulting LLC with none of the consulting in relation to the indication of pain). B. I. Karp declares no conflict of interest. R. D. Kerns reports honoraria for presentation at the IMMPACT consensus meeting that informed this manuscript; research grants from NIH, PCORI, and VA paid to his institution; a consulting fee for a NIH-sponsored research grant; a honorarium for planning and participation in an IMMPACT consensus conference on patient engagement in clinical pain research; honoraria for participation in NIH and PCORI DSMBs and a honorarium for participation as member of Scientific Advisory Board, Chronic Pain Centre of Excellence for Canadian Veterans; an unpaid role on the Board of Directors, A Place to Nourish your Health; and an honorarium for role as the Executive Editor, Pain Medicine. B. A. Kleykamp reports income from ACTTION as a full-time employee October 2018-August 2021; being the owner and principal of BAK and Associates, LLC a research and science writing consulting firm; contracts to BAK and Associates, LLC over the past 36 months include STATinMED, American Society of Addiction Medicine, ECRI, Hayes/Symplr, Pinney Associates, and Palladian Associates; payments and honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from University of Kentucky, STATinMED, Filter magazine, and Virginia Commonwealth University; support for attending meetings or travel from University of Kentucky and Virginia Commonwealth University; and a role as Communications Chair for the College on Problems of Drug Dependence. J. D. Loeser reports no conflict of interest. S. Mackey reports support for the present manuscript from the National Institutes of Health, U.S. Food and Drug Administration, Patient-Centered Outcomes Research Institute, Chris Redlich Professorship in Pain Research, and Dodie and John Rosekrans Pain Research Endowment Fund (all through Stanford University); consulting fees from Oklahoma University-Smith NIH Grant; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Memorial Sloan Kettering Cancer Center, National Institutes of Health, Washington University, Oakstone Publishing, Comprehensive Review of Pain Medicine CME Lecture Series, Walter Reed AFB, Web-Based Lecture, Bull Publishing, George Washington University, University of Washington, Veterans Affairs, HSRD Naloxone Distribution IIR Advisory Board, Canadian Pain Society, National Institutes of Health, and New York University; support for attending meetings or travel from American Academy of Pain Medicine, American Society of Regional Anesthesia and Pain Medicine, Washington University, George Washington University, National Institutes of Health, University of Washington, U.S. Federal Drug Administration, New York University, Weill Cornell Medical College, and the International Neuromodulation Society (INS); roles on the Drug Safety and Risk Management Advisory Committee, Anesthetic and Analgesic Drug Products Advisory Committee (DSaRM/AADPAC)/(FDA) (unpaid role as Advisor"

"The first author was renumerated by IMMPACT for their work at the consensus meeting and in drafting the manuscript. The project was supported by ACTTION, a public–private partnership. The views expressed in this article are those of the authors and no official endorsement by the Food and Drug Administration (FDA) or the pharmaceutical and device companies that provided unrestricted grants to support the activities of the ACTTION public–private partnership should be inferred. Individual authors' declarations of potential conflicts of interest are as follows: M. J. Bair reports grants or contracts from VA Health Services Research and Development, VA Cooperative Studies Program, and National Endowment for the Arts and participation on a Data Safety Monitoring Board or Advisory Board on a NIH project conducted at the University of Utah. This trial is a pragmatic trial of physical therapy intervention. Prof Cherkin reports being paid an honorarium for mentoring the first author with manuscript writing. L. L. DeBar reports support for the present manuscript from Kaiser Permanente Washington Health Research Institute (KPWHRI); grants and contracts from National Institutes of Health (NIH) and Patient-Centered Outcomes Research Institute (PCORI); an honorarium for a lecture at 2020 IMMPACT Consensus Meeting; support for attending meetings from KPWHRI and NIH; and participation on a Data Safety Monitoring Board or Advisory Board for NCCIH, BACPAC DSMB. P. Cowan is the co-founder and secretary of the World Patients Alliance and Board Member Emeritus as well as Founder of the American Chronic Pain Association. P. Desjardins reports grants or contracts from the NIH/NIDCR Opioid Analgesic Reduction Study as co-investigator; consulting fees from Acadia Pharmaceuticals, GlaxoSmithKline Consumer Healthcare, Neurana Pharmaceuticals, Bayer Consumer Healthcare, Senju USA, Antibe Therapeutics, and CenExel; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer Consumer Healthcare; participation on the GSK Consumer Advisory Board; and roles on the Board of Directors of ProSelect/Coverys Medical Liability Insurance and the Board of Governors of South Orange Performing Arts Center. R. H. Dworkin has received in the past 5 years research grants and contracts from the U.S. Food and Drug Administration and the U.S. National Institutes of Health, and compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CombiGene, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, GlaxoSmithKline, Glenmark, Gloriana, Grace, Hope, Hospital for Special Surgery, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, Orion, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG. R. R. Ewards reports no conflicts of interest. J. T Farrar reports grants or contracts from the NIH-NCATS-UL1 Grant (Co-I), FDA-BAA Contract, NIH-NIDDK-U01 Grant (CoI), and NIH-NINDS-U24 Grant (PI); consulting fees from Lilly and Vertex Pharma; participation on a Data Safety Monitoring Board or Advisory Board for NIH-NIA(DSMB); and a role as President-Elect US-ASP. M. Ferguson reports grants or contracts from ACTTION paid to her institution for work on systematic reviews and payment or honoraria for lectures at IMMPACT meetings from ACTTION. R. Freeman reports consulting fees from AlgoRx, Allergan, Applied Therapeutics, Clexio, Collegium, Cutaneous NeuroDiagnostics, Glenmark, GW Pharma, GlaxoSmithKline, Eli Lilly, Lundbeck, Maxona, Novartis, NeuroBo, Regenacy, Vertex, and Worwag and stock options in Cutaneous Neurodiagnostic Life Sciences, NeuroBo, Maxona, and Regenacy. J. S. Gewandter reports grants or contracts from the NIH; consulting fees from AlgoTX, GW Pharma, Magnolia Neurosciences, Orthogonal, Science Branding Consulting, AKP Pharma, and Eikonizo and support for attending meetings or travel from SOPATE and INS. I. Gilron declares a travel stipend to attend ACTTION meeting 2019 and reports consulting fees from CombiGene, GW Research, Lilly, and Novaremed. H. Grol-Prokopczyk reports grants or contracts from the National Institute on Aging of the National Institutes of Health, Award #R01AG065351; honoraria for an invited lecture for Multidisciplinary Research in Gerontology Colloquium Series, University of Southern California, and for an invited lecture at Napa Pain Conference; and travel reimbursement for travel to Napa Pain Conference. S. H. Hertz declares consulting fees from Adial Pharmaceuticals, AIXThera Operations Limited, Asahi Kasei Pharma America Corporation, Allay Pharmaceuticals, Amygdala Neurosciences, Araim Pharmaceuticals, Artugen Therapeutics, Avenue Therapeutics, BioQ Pharma, Cali Pharmaceuticals, Celero Pharma, Centrexion Therapeutics, Collegium Pharmaceutical, Concentric Analgesics, Currax Pharmaceuticals, Delpor, Domain Therapeutics, Enalare Therapeutics, Go Medical Industries, Heron Pharmaceuticals, Innocoll Biotherapeutics, Intra-Cellular Therapies, Kaleo, Lyndra Therapeutics, Maxona Pharmaceuticals, MDI Pharma, Nema Research, Neuroderm, Neumentum, Novilla Pharmaceuticals, OncoZenge, Pfizer, PleoPharma, SafeRx Pharmaceuticals, The Scripps Research Institute, Sollis Therapeutics, Sparian Biosciences, Teikoku Pharma USA, Taiwan Liposome Company, Tremeau Pharmaceuticals, Vallon Pharmaceuticals, Vizuri Health Sciences, and WinSanTor. D. G. Hohenschurz-Schmidt reports support for the present manuscript from a PhD studentship by the Alan and Sheila Diamond Charitable Trust and a honorarium from IMMPACT; a research grant from The osteopathic Foundation (paid to institution); consulting fees from Altern Health Ltd; and the role of executive committee member of the Society for Back Pain Research. S. Iyengar reports employment and travel support from the NINDS/NIH; stock options in Retiree and Eli Lilly and Company; and other financial or nonfinancial interests through employee of NINDS/NIH and adjunct senior research professor, Indiana University School of Medicine, Departments of Anesthesia and Clinical Pharmacology. C. Kamp reports support for the present manuscript from ACTTION, FDA contract #HHSF223201000078C, with payments made directly to her institution, University of Rochester Medical Center, providing 5% salary support and consulting fees from Clintrex Research Corporation (payments made to her consulting company CLKamp Consulting LLC with none of the consulting in relation to the indication of pain). B. I. Karp declares no conflict of interest. R. D. Kerns reports honoraria for presentation at the IMMPACT consensus meeting that informed this manuscript; research grants from NIH, PCORI, and VA paid to his institution; a consulting fee for a NIH-sponsored research grant; a honorarium for planning and participation in an IMMPACT consensus conference on patient engagement in clinical pain research; honoraria for participation in NIH and PCORI DSMBs and a honorarium for participation as member of Scientific Advisory Board, Chronic Pain Centre of Excellence for Canadian Veterans; an unpaid role on the Board of Directors, A Place to Nourish your Health; and an honorarium for role as the Executive Editor, Pain Medicine. B. A. Kleykamp reports income from ACTTION as a full-time employee October 2018-August 2021; being the owner and principal of BAK and Associates, LLC a research and science writing consulting firm; contracts to BAK and Associates, LLC over the past 36 months include STATinMED, American Society of Addiction Medicine, ECRI, Hayes/Symplr, Pinney Associates, and Palladian Associates; payments and honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from University of Kentucky, STATinMED, Filter magazine, and Virginia Commonwealth University; support for attending meetings or travel from University of Kentucky and Virginia Commonwealth University; and a role as Communications Chair for the College on Problems of Drug Dependence. J. D. Loeser reports no conflict of interest. S. Mackey reports support for the present manuscript from the National Institutes of Health, U.S. Food and Drug Administration, Patient-Centered Outcomes Research Institute, Chris Redlich Professorship in Pain Research, and Dodie and John Rosekrans Pain Research Endowment Fund (all through Stanford University); consulting fees from Oklahoma University-Smith NIH Grant; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Memorial Sloan Kettering Cancer Center, National Institutes of Health, Washington University, Oakstone Publishing, Comprehensive Review of Pain Medicine CME Lecture Series, Walter Reed AFB, Web-Based Lecture, Bull Publishing, George Washington University, University of Washington, Veterans Affairs, HSRD Naloxone Distribution IIR Advisory Board, Canadian Pain Society, National Institutes of Health, and New York University; support for attending meetings or travel from American Academy of Pain Medicine, American Society of Regional Anesthesia and Pain Medicine, Washington University, George Washington University, National Institutes of Health, University of Washington, U.S. Federal Drug Administration, New York University, Weill Cornell Medical College, and the International Neuromodulation Society (INS); roles on the Drug Safety and Risk Management Advisory Committee, Anesthetic and Analgesic Drug Products Advisory Committee (DSaRM/AADPAC)/(FDA) (unpaid role as Advisory Committee Member) and for HSR"